Journal article
Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial
Nature medicine, PMID 9502015
01/16/2026
DOI: 10.1038/s41591-025-04141-4
PMID: 41545592
Abstract
Systemic treatments are limited for patients with meningiomas that have progressed after surgery or radiation. Loss of NF2 and CDKN2A/CDKN2B is common in higher-grade meningiomas and promotes progression in preclinical models. We evaluated the efficacy of abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, as one arm of the Alliance umbrella trial A071401, a genomically driven phase 2 study in recurrent and progressive meningiomas. Eligible patients with grade 2 or 3 tumors and NF2 mutations or CDK pathway alterations were treated with abemaciclib. Two co-primary endpoints were used: progression-free survival at 6 months (PFS6) and response rate as defined by local review; the trial would be declared positive if either endpoint was met. The success threshold for PFS6 was 8 or more of 24 patients; for the response rate, it was 3 or more of 24 patients. Ninety-six patients were screened and 36 patients received treatment. The mean number of treatment cycles was nine and the median follow-up was 21 months. The first 24 patients who met the eligibility criteria and began treatment could be evaluated for the primary endpoint. The observed PFS6 rate was 58% (14 of 24 patients, 95% confidence interval = 37-78%), thus meeting the PFS6 criteria for promising activity. The best response was stable disease in 16 of 24 patients. Of the 36 patients who started treatment, nine had a grade 3 and two had grade 4 adverse events at least possibly related to treatment. Grade 4 toxicities included alanine aminotransferase elevation (1), aspartate aminotransferase elevation (1) and vomiting (1). The trial met its primary endpoint. Abemaciclib was well tolerated and resulted in improved PFS6. Abemaciclib warrants further investigation for patients with progressive grade 2 or 3 meningiomas harboring NF2 or CDK pathway alterations. ClinicalTrials.gov registration no. NCT02523014 .
Details
- Title: Subtitle
- Abemaciclib in meningiomas with somatic NF2 or CDK pathway alterations: the phase 2 Alliance A071401 trial
- Creators
- Priscilla K Brastianos - Massachusetts General HospitalKatharine Dooley - Mayo ClinicSusan Geyer - Mayo ClinicElizabeth R Gerstner - Massachusetts General HospitalTimothy J Kaufmann - Mayo Clinic in ArizonaA John Iafrate - Massachusetts General HospitalMaria Martinez-Lage - Massachusetts General HospitalMohammed Milhem - University of IowaMary Roberta Welch - Columbia University Irving Medical CenterThomas J Kaley - Memorial Sloan Kettering Cancer CenterJan Drappatz - UPMC Hillman Cancer CenterAmy Chan - Dartmouth–Hitchcock Medical CenterPriya Kumthekar - University of ChicagoCarlos Kamiya Matsuoka - The University of Texas MD Anderson Cancer CenterRoy E Strowd - Wake Forest UniversityAdam L Cohen - Virginia Cancer InstituteKurt Jaeckle - Mayo Clinic in FloridaLindsay Robell - University of MichiganRajiv S Magge - Cornell UniversityJoo Yeon Nam - Rush University Medical CenterNicholas Blondin - Smilow Cancer HospitalNawal Shaikh - University of Mississippi Medical CenterIan Rabinowitz - New Mexico Cancer CenterAlissa A Thomas - University of Vermont Medical CenterDavid E Piccioni - UC San Diego Health SystemPaul Brown - Mayo Clinic in ArizonaStefan Kaluziak - Massachusetts General HospitalElizabeth Codd - Massachusetts General HospitalDaniel P Cahill - Massachusetts General HospitalSandro Santagata - Dana-Farber Cancer InstituteFrederick G Barker II - Massachusetts General HospitalEvanthia Galanis - Mayo Clinic in Arizona
- Resource Type
- Journal article
- Publication Details
- Nature medicine, PMID 9502015
- DOI
- 10.1038/s41591-025-04141-4
- PMID
- 41545592
- NLM abbreviation
- Nat Med
- ISSN
- 1546-170X
- eISSN
- 1546-170X
- Publisher
- NATURE PORTFOLIO; BERLIN
- Grant note
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)GlaxoSmithKline (GlaxoSmithKline plc.)Eli Lilly and Company (Lilly)Damon Runyon Cancer Research Foundation (Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation)
The research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (NIH) under award nos. U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA189960, UG1CA189824, UG1CA232760, UG1CA233180, UG1CA233184, UG1CA233290, UG1CA233329, UG1CA189816, UG1CA189856, UG1CA233160, UG1CA233323, UG1CA233337; U10CA180868 and UG1CA189867 (NRG Oncology); and U10CA180888 (Southwest Oncology Group). It was also supported in part by funds from AstraZeneca, Eli Lilly, GlaxoSmithKline and the Damon Runyon Cancer Research Foundation (P.K.B.), and a philanthropic grant from Alexandra Drane (P.K.B.). P.K.B. receives funding from the National Brain Tumor Society, NIH, the American Association for Cancer Research, the Melanoma Research Alliance, a Terry and Jean de Gunzburg MGH Research Scholar Award, the Breast Cancer Research Foundation, the Hellenic Women's Club (Demetra Fund) and Alexandra Drane. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. A full list of companies who have provided support to Alliance for Clinical Trials in Oncology and Alliance Foundation Trials programs can be found at https://acknowledgments.alliancefound.org.
- Language
- English
- Electronic publication date
- 01/16/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985121598302771
Metrics
1 Record Views